4ia0

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Crystal structure of the PDE5A1 catalytic domain in complex with novel inhibitors

Structural highlights

4ia0 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.17Å
Ligands:5BB, MG, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PDE5A_HUMAN Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP.

Publication Abstract from PubMed

The substituents both at the 6-position of the 5-bromopyrimidinone ring and at the 5'-position of the phenyl ring of 5-bromopyrimidin-4(3H)-ones were explored. 5-Bromo-6-isopropyl-2-(2-propoxy-phenyl)pyrimidin-4(3H)-one was identified as a new scaffold for potent PDE5 inhibitors. The crystal structures of PDE5/2e and PDE5/10a complexes provided a structural basis for the inhibition of 5-bromopyrimidinones to PDE5. In addition, it was also found that there is a great tolerance for the substitution at the 5'-position of the phenyl ring of 5-bormopyrimidinones and the resulted compound 13a has the highest inhibition activity to PDE5 (IC50, 1.7 nM).

Exploration of the 5-bromopyrimidin-4(3H)-ones as potent inhibitors of PDE5.,Gong X, Wang G, Ren J, Liu Z, Wang Z, Chen T, Yang X, Jiang X, Shen J, Jiang H, Aisa HA, Xu Y, Li J Bioorg Med Chem Lett. 2013 Sep 1;23(17):4944-7. doi: 10.1016/j.bmcl.2013.06.062. , Epub 2013 Jun 29. PMID:23867165[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
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Application of ITC-Based Characterization of Thermodynamic and Kinetic Association of Ligands With Proteins in Drug Design.
Su et al. (2018)
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See Also

References

  1. ↑ Gong X, Wang G, Ren J, Liu Z, Wang Z, Chen T, Yang X, Jiang X, Shen J, Jiang H, Aisa HA, Xu Y, Li J. Exploration of the 5-bromopyrimidin-4(3H)-ones as potent inhibitors of PDE5. Bioorg Med Chem Lett. 2013 Sep 1;23(17):4944-7. doi: 10.1016/j.bmcl.2013.06.062. , Epub 2013 Jun 29. PMID:23867165 doi:http://dx.doi.org/10.1016/j.bmcl.2013.06.062

Contents


PDB ID 4ia0

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OCA

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